The Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations

NCT ID: NCT00286897

Last Updated: 2015-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 702 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2007-08-31

Brief Summary

Patients will be randomised to receive either placebo or the study drug for a period of 30 weeks, in addition to their standard Parkinsonian medications. During the first 8 weeks, the patient's levodopa doses may be adjusted if necessary by the investigator. For the remainder of the 22 weeks, all medications should be kept stable. Patients will be required to attend the clinic twice during the screening period and then a further 8 times during the treatment period. They will be required to complete home diaries where they will record their motor function. In addition, their doctor will assess their Parkinson's disease during the clinic visits. There will also be blood draws for safety and pharmacokinetic and pharmacogenomics evaluation. Following the treatment and assessment period, they will return to the clinic one month later for follow up.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

E2007

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female patients with idiopathic PD fulfilling the (UK) Parkinson's disease Society Brain Bank diagnostic criteria, with a good response to levodopa.

2. Patients must have been diagnosed with idiopathic PD at >= 30 years of age.

3. Patients must have predictable motor fluctuations of the wearing OFF type with the presence of at least 2 hours of OFF time during the waking day (excluding the morning OFF time) as evidenced by diary cards completed at screening and confirmed by diary data collected at the baseline visit.

4. Before patients are randomised they must be able to show that they are able to accurately complete the diary cards. During the diary-training period at the initial screening visit there must be diary evidence of at least one transition of OFF to ON or from ON to OFF and patients must show 75% concordance with Investigator's completion of the diary card.

5. Patients must rate between II-IV on the Hoehn & Yahr scale when in an OFF state.

6. Patients must be taking optimised levodopa therapy (according to investigator's opinion) at least 3 times during the waking day (not including bedtime/night time dose) up to a maximum of 8 doses daily (includes bedtime/night time dose).

7. Patients who are treated with dopamine agonists, COMT inhibitors or MAOB inhibitors and other anti-PD drugs must be on optimised and stable doses for at least 4 weeks prior to initial screening visit and must remain stable throughout the study. Only levodopa dosage can be adjusted downwards in the first 8 weeks of the double-blind treatment phase.

8. In the Investigator's opinion patients must be able to distinguish their own motor states and the absence or presence of troublesome or non-troublesome dyskinesias.

9. In the Investigator's opinion patients are able to complete the study including the completion of the home diary cards and capable of giving full written informed consent.

Exclusion Criteria

1. Pregnant or lactating women.

2. Women of child bearing potential unless infertile (including surgically sterile) or practicing effective contraception (e.g., abstinence, IUD or barrier method plus hormonal method). These patients must have a negative serum B-HCG test at the initial screening visit (Visit 1), and a negative urine pregnancy test at the Baseline visit (Visit 3). These patients must also be willing to remain on their current form of contraception for the duration of the study. Postmenopausal women may be recruited but must be amenorrhoeic for at least 1 year to be considered of non-child bearing potential as determined by the investigator.

3. Fertile men not willing to use reliable contraception and fertile men with partners not willing to use reliable contraception.

4. Patients with a past or present history of drug or alcohol abuse as per DSM IV criteria.

5. Patients with a past (within one year) or present history of psychotic symptoms requiring antipsychotic treatment. Patients may be taking anti-depressant medication, however the dose must be stable for 4 weeks prior to the baseline visit. Use of anti-psychotic medication including clozapine and quetiapine is prohibited even if the indication is for movement disorders.

6. Patients with a past (within one year) or present history of suicidal ideation or suicide attempts.

7. Patients with unstable abnormalities of the hepatic, renal, cardiovascular, respiratory, gastro-intestinal, haematological, endocrine or metabolic systems which might complicate assessment of the tolerability of the study medication.

8. Patients with significantly elevated liver enzymes (abnormal bilirubin or serum transaminase levels of more than 1.5 times the upper normal limit).

9. Patients with current or prior treatment (within 4 weeks prior to the baseline visit) with medication known to induce the enzyme cytochrome P450 3A4.

10. Current or prior treatment (within 4 weeks prior to the baseline visit) with tolcapone, methyldopa, budipine, reserpine, seroquel or intermittent use of either liquid forms of levodopa or subcutaneous apomorphine.

11. Patients with previous stereotactic surgery (eg pallidotomy) for Parkinson's disease or with planned stereotactic surgery during the study period.

12. Patients receiving or with planned (next 6 months) deep brain stimulation.

13. Patients who have received an investigational product within 4 weeks prior to the screening visit or patients that have participated in a previous study with E2007.

14. Patients with clinically significant cognitive impairment (MMSE <24 and /or fulfilling DSM IV criteria for dementia due to Parkinson's disease).

15. Patients with conditions affecting the peripheral or central sensory system unless related to Parkinson's disease (such as mild sensory or pain syndromes limited to OFF periods) that could interfere with the evaluation of any such symptoms caused by the study drug.

16. Patients with any condition that would make the patient, in the opinion of the Investigator, unsuitable for the study.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Limited

INDUSTRY

Sponsor Role: lead

Principal Investigators

Alessia Nicotra, MD, PhD, DIC

Role: STUDY_DIRECTOR

Eisai Limited

Locations

University Clinic Innsbruck

Innsbruck, , Austria

Department of Neurology

Vienna, , Austria

Cliniques Universitaires St-Luc

Brussels, , Belgium

C.H.U.de Charleroi

Charleroi, , Belgium

U.Z. Antwerpen

Edegem, , Belgium

U.Z. Gent

Ghent, , Belgium

C.H.R. de la Citadelle

Liège, , Belgium

Hopital St-Pierre

Ottignies, , Belgium

St-Andries Ziekenhuis

Tielt, , Belgium

University Hospital

Olomouc, , Czechia

University Hospital

Ostrava, , Czechia

Pliklinika Modry Pavilon

Ostrava, , Czechia

Nemocnice Pardubice

Pardubice, , Czechia

FN Plzen

Pilsen, , Czechia

Nemocnice Pisek

Plsek, , Czechia

Fakultni nemocnice Kralovske Vinohrady

Prague, , Czechia

VFN Praha

Prague, , Czechia

Parnu Hospital

Pärnu, , Estonia

West Tallinn Central Hospital

Tallinn, , Estonia

Tartu University Hospital

Tartu, , Estonia

Centre Hospitalier du Pays d'Aix

Aix-en-Provence, , France

Service Neurologie

Bayonne, , France

CHU Gabrief Montpied

Clermont-Ferrand, , France

Contis, Patrick

Colomiers, , France

Lille, , France

Centre de Pharmacologie Clinique et Evaluation Therapeutique

Marseille, , France

Nantes, , France

Hopital de la Pitie Salpetriere

Paris, , France

Centre d'Investigation Clinique, Hospital Purpan

Toulouse, , France

Kliniken Beelitz GmbH

Beelitz-Heilstätten, , Germany

Uni-klinikum Charite, Campus Virchow-klinikum

Berlin, , Germany

Bochum, , Germany

Universitaetsklinikum Carl Gustav Carus

Dresden, , Germany

Neurologische Universitatsklinik

Göttingen, , Germany

Universitatkrankenhaus Hamburg Eppendorf

Hamburg, , Germany

Hanau, , Germany

Hanover, , Germany

Paracelsus-Elena-Klinik

Kassel, , Germany

Gertrudis-Klinik, Parkinson Klinik

Leun-Biskirchen, , Germany

Universitatsklinik Lubeck Klinik fur Neurologie Ratzeburger Allee 160 D-23538 Lubeck

Lübeck, , Germany

Klinik fuer Neurologie

Marburg, , Germany

Technische Universitaet Muenchen

München, , Germany

LMU Munchen, Neurologische Universitatsklinik

München, , Germany

Tübingen, , Germany

Wiesbaden, , Germany

Clinexpert SMO, Budapest

Budapest, , Hungary

St. Imre Hospital

Budapest, , Hungary

Semmelweis University

Budapest, , Hungary

Uzsoki Street Hospital

Budapest, , Hungary

Jahn Ferenc Hospital

Budapest, , Hungary

B-A-Z County Hospital

Budapest, , Hungary

Budapest, , Hungary

A Petz Hospital

Győr, , Hungary

Nyiro Gyula Hospital

Győr, , Hungary

Jahn Ferenc Del-Pesti Hospital

Miscolc, , Hungary

Cham Sheba Medical Center

Haifa, , Israel

Rabin MC

Petah Tikva, , Israel

Ichilov Sourasky MC

Petah Tikva, , Israel

Rambam Healthcare Center

Ramat Gan, , Israel

Carmel Medical Center

Tel Aviv, , Israel

Assaf Harofe Medical Center

Zerafin, , Israel

Ospedal Villa Margherita

Arcugnano, , Italy

Universita degli Studi di Genova

Genova, , Italy

Ospedale della Misericordia

Grosseto, , Italy

Policlinico Umberto I

Grosseto, , Italy

Ospedale Versillia

Lido di Camaiore, , Italy

Universita degli Studi Federico II

Napoli, , Italy

IRCSS Fondazione Casimiro Mondino

Pavia, , Italy

Ospedale Civile di Pescara

Pescara, , Italy

Ospedale San Giovanni Battista

Roma, , Italy

Roma, , Italy

Kaunas Medical University Hospital

Kaunas, , Lithuania

Vilnius University Emergency Hospital

Vilnius, , Lithuania

Vilnius University Hospital, Santariskiu Clinic

Vilnius, , Lithuania

Nzoz Kendrion

Bialystok, , Poland

PSK Klinika Neurologii

Bialystok, , Poland

Klinika Neurologii Doroslych AM

Gdansk, , Poland

Centralny Szpital Kliniczny

Katowice, , Poland

WSS im. Kardynala S. Wyszynskiego

Lublin, , Poland

Lublin, , Poland

Indywidualna Specjalistyczna Praktyka Lekarska, Gabinet Neur

Mosina k/Poznania, , Poland

Specjalistyczna Przychodnia Lekarska

Płock, , Poland

Centralny Szpital Kliniczny MSwia

Warsaw, , Poland

Warsaw, , Poland

Centrum Leczenia Chorob

Warsaw, , Poland

Servico de Neurologia

Coimbra, , Portugal

Hospital Santa Maria

Lisbon, , Portugal

Hospital Santo Antonio

Porto, , Portugal

Clinic of Neurology and Psychiatry

Belgrade, Serbia and Montenegro, , Serbia

Clinic of Neurology

Belgrade, Serbia and Montenegro, , Serbia

Institute of Neurology

Belgrade, Serbia and Montenegro, , Serbia

407 Medi Clinic

Bloemfontein, , South Africa

Rosepark Hospital

Bloemfontein, , South Africa

Groote Schuur Hospital

Cape Town, , South Africa

Christian Barnard Memorial Hospital

Cape Town, , South Africa

406 Claremont Hospital

Cape Town, , South Africa

Morningside, Johannesburg, , South Africa

Panorama Medi-Clinic

Parow, , South Africa

Wilgers Medical Centre

Pretoria, , South Africa

Sunninghill Hospital

Sunninghill, Johannesburg, , South Africa

Umhlanga Hospital

Umhlanga, , South Africa

Hospital Clinic I Provincial

Barcelona, , Spain

Hospital de sant Pau

Barcelona, , Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital del Mar, Servei de Neurologia

Barcelona, , Spain

Hospital Ramon y Cajal

Madrid, , Spain

Hospital Puerta de Hierro

Madrid, , Spain

Clinica Universitaria de Navarra

Pamplona, , Spain

Hospital Clinico Universitario de Santiago

Santiago de Compostela, , Spain

Praktiken Ankaret

Karlstad, , Sweden

St Gorans Sjukhus

Stockholm, , Sweden

Bupa Flyde Coast Hospital

Blackpool, , United Kingdom

North Surrey Primary Care Trust

Chertsey, , United Kingdom

District General Hospital NHS Trust

Clwyd, , United Kingdom

North Manchester General Hospital

Crumpsall, , United Kingdom

Royal Free Hospital

London, , United Kingdom

University College Hospital

London, , United Kingdom

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Countries

Austria; Belgium; Czechia; Estonia; France; Germany; Hungary; Israel; Italy; Lithuania; Poland; Portugal; Serbia; South Africa; Spain; Sweden; United Kingdom

Other Identifiers

2005-004314-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E2007-E044-301

Identifier Type: -

Identifier Source: org_study_id